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Optimization of Chitosan-Based Polyelectrolyte Nanoparticles for Gene Delivery, Using Design of Experiment: In Vitro and in Vivo Study Publisher Pubmed



Baghaei M1 ; Tekie FSM2 ; Khoshayand MR3 ; Varshochian R2 ; Hajiramezanali M4 ; Kachousangi MJ5 ; Dinarvand R1, 2 ; Atyabi F1, 2
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Drug & Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of medical sciences, Tehran, Iran

Source: Materials Science and Engineering C Published:2021


Abstract

Gene therapy is a novel approach for cancer treatment and investigation for suitable gene delivery systems is remarkable. Here, preparation of a polyelectrolyte complex containing polysaccharides: trimethyl chitosan (TMC) as the positive and hyaluronate (HA), dextran sulfate and alginate as the negative part was studied. The optimized nanoparticles (TMC: between 0.2 and 0.47 mg/ml, HA: 0.35 mg/ml (≈131 nm, nearly full gene loading)) were obtained via primary screening followed by the D-optimal method. In vitro cellular study on the MCF7 cell line confirmed the non-toxicity and high cellular uptake (>90%) of prepared nanoparticles. Notably, in vivo study indicated noticeable tumor uptake of nanoparticles while low accumulation in vital organs such as heart, liver and lungs. Moreover, although a qualitative variable was considered, the applied method restricted the number of runs by selecting spots from the spherical atmosphere. The prepared nanoparticles could be suggested as an efficient and safe delivery system for cancer gene delivery. © 2020